PXD038364 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Monitoring α-synuclein ubiquitination dynamics reveals key endosomal effectors mediating its trafficking and degradation |
Description | While defective α-synuclein homeostasis is central to the pathogenesis of Parkinson’s, fundamental questions about its intracellular trafficking remain unresolved. We have developed a bimolecular fluorescence complementation assay in living cells to monitor de novo ubiquitination of α-synuclein. We identified lysine residues 45, 58 and 60 as critical ubiquitination sites for the degradation of α-synuclein. This is mediated by NBR1 binding to ubiquitinated α-synuclein and entry into endosomes in a process that involves ESCRT I-III complexes for subsequent lysosomal degradation. Autophagy or the autophagic chaperone Hsc70 are dispensable for this pathway. Antibodies against diglycine-modified α-synuclein peptides confirmed that endogenous α-synuclein is similarly ubiquitinated in brain and targeted to the lysosome in rat primary and human iPSC-derived neurons. Ubiquitinated α-synuclein was detected in Lewy bodies and cellular models of aggregation suggesting that it may be entrapped with endo/lysosomes in inclusion bodies. Collectively, our data elucidate the intracellular trafficking of de novo ubiquitinated α-synuclein and provide the tools for investigating the rapidly turned-over fraction of this disease-causing protein. |
HostingRepository | PRIDE |
AnnounceDate | 2023-05-17 |
AnnouncementXML | Submission_2023-05-17_06:49:55.850.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | RomanFischer |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | ubiquitinylated lysine |
Instrument | Orbitrap Fusion Lumos; Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-11-25 07:02:48 | ID requested | |
⏵ 1 | 2023-05-17 06:49:56 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Ubiquitination, degradation, Parkinson's, homeostasis,α-synuclein |
Contact List
RomanFicher |
contact affiliation | Discovery Proteomics Facility Target Discovery Institute University of Oxford |
contact email | roman.fischer@ndm.ox.ac.uk |
lab head | |
RomanFischer |
contact affiliation | University of Oxford |
contact email | roman.fischer@ndm.ox.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/05/PXD038364 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD038364
- Label: PRIDE project
- Name: Monitoring α-synuclein ubiquitination dynamics reveals key endosomal effectors mediating its trafficking and degradation